Reflecting the advent of the so-called "high-age" society, it has become a serious public concern to develop medical measures for treatment of senile dementia as caused by damages or disturbances of the cerebral functions which are, in turn, attributable to cerebrovascular diseases or damages or disturbances of intracerebral energy metabolism. A variety of drugs have heretofore been developed as anti-dementia drugs. At the present status, senile dementia, and amnesia as caused by cerebrovascular diseases as well as the biological mechanisms of occurrence of these disorders or diseases have not yet been elucidated fully. In these circumstances, no sufficient clue has yet been established to discover and screen effective cerebral drugs. As experimental methods for inducing amnesia in normal mammalian animals, it is known to administer such an agent which inhibits the in vivo synthesis of nucleic acids or proteins, or an anticholinergic agent. Amnesia is also known to be inducible by cerebral anoxia, ischemic load or the like. With using such model animals which have amnesia induced by these causative agents, it has been attempted to detect and develop cerebral drugs which are capable of amelioratively treating or preventing the amnesia. In addition, with using such model animals which have cerebral anoxia induced either by giving a lethal dose of potassium cyanide or by subjecting to hypobaric or normobaric hypoxic conditions, namely, the reduced oxygen-supply conditions, attempts have also been made to develop cerebral drugs which are effective for the improvement or amelioration of cerebral circulation metabolism or intracerebral energy metabolism. These matters are referred to e.g. in "Folia Pharmacol. Japan", 85, 323-328 (1985); ibid., 86, 445-456 (1986): and Japanese Patent Application first publication "Kokai" No. 117468/79 or its corresponding U.S. Pat. No. 4,369,139.
It is well accepted that oxygen deprivation is one of the most damaging conditions affecting the animal or human brain, and that when oxygen supply to the brain becomes deficient, cerebral functions cease after brief periods of cerebral anoxia and tissue destruction ensues. Consequently, any suitable agents which enable the brain to withstand even mild degree of cerebral anoxia would be expected to be useful as a cerebral protective agent or a drug for improving or ameliorating the damaged or disturbed cerebral functions of brain (the drug of this utility is hereinafter sometimes merely called as "a cerebral drug"). Many compounds have been investigated for their cerebral protective effect on cerebral anoxia which is experimentally induced by subjecting the animal to hypoxic conditions, whereby there is obtained a suggestion or indication that the tested compounds are effective for treatment of cerebral anoxic or ischemic diseases or disorders (see, e.g. "Arch. int. Pharmacodyn." 233, 136-144 (1978) and "Life Science" 13, 467-474 (1973)).
However, the cerebral drugs which have been provided so far can hardly be said to have fully satisfactory effects and proven reliability. Under these circumstances, there remains a demand for the development of new cerebral drugs which are still stronger and safer than the known drugs as provided to date.
An object of this invention is to prepare and provide novel compounds having excellent pharmacological effects for the improvement of the damaged or disturbed cerebral functions of the brain as well as a high level of safety with being free of side effects. Another object of this invention is to provide novel cerebral drugs. To achieve these objects, we, the present inventors, and our associates have proceeded with extensive investigations. As a result, we have found that compounds having anti-anoxia effects, in other words, cerebral protective effect against cerebral anoxia are useful or promising as drugs having medicinal effects capable of treating cerebration disorders of mammals, including human, when such compounds are effective in significantly prolonging the survival time of mice having cerebral anoxia experimentally induced under hypobaric hypoxia conditions in the experiments wherein the cerebral anoxia mice are used as model animals. We and our associates already tested the cerebral protective effect against cerebral anoxia of some known N,N-dialkyloxamic acids (which may also be called N,N-dialkyloxaminic acids) which are disclosed in Japanese Patent Application first publication "Kokai" No. 24823/79. Moreover, we also synthetized another N,N-di-substituted oxamic acid compounds and assayed the cerebral protective effect of these another compounds against cerebral anoxia.
As a result of our above-mentioned earlier investigations and tests, we already found that N,N-di-alkyl-substituted or N,N-di-alkenyl-substituted oxamic acid compounds which may generally be represented by the following formula (A): ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different and are individually a linear or branched alkyl group of 1 to 4 carbon atoms or an alkenyl group of 2 to 4 carbon atoms, or a pharmacologically acceptable salt thereof have the cerebral protective effect against cerebral anoxia and low toxicity, as well as their potential usefulness as the cerebral drugs (see Japanese patent application No. 164,938/88 or its corresponding European patent application No. 89306780.1 and its published specification No. 0350260A2 published Jan. 10, 1990 or its corresponding U.S. patent application Ser. No.373,469 filed on Jun. 30, 1989, pending).
In addition to our previous investigation about the N,N-di-alkyl-substituted or N,N-di-alkenyl-substituted derivatives of oxamic acid as represented by the above general formula (A), we, the present inventors, have now developed our investigations in an attempt to synthetize further novel N-mono-substituted or N,N-di-substituted derivatives of oxamic acid, and we have now succeeded in synthetizing as the new componds an N-(dialkylaminoalkyl)-substituted or N-(dialkylaminoalkyl)-N-alkyl-substituted oxamic acid compound having a general formula (I) described below. Furthermore, we have assayed this new N-mono-substituted or N,N-di-substituted oxamic acid compound of the formula (I) as synthetized, for its cerebral protective effect against cerebral anoxia.
As an outcome of our recent investigations and tests as above, we have now discovered that the new N-(dialkylaminoalkyl)-substituted or N-(dialkylaminoalkyl)-N-alkyl-substituted oxamic acid compound having the general formula (I) as described below exhibits the cerebral protective effect against cerebral anoxia and low toxicity, similarly to the N,N-dialkyl-substituted or N,N-di-alkenyl-substituted oxamic acid compound of the above formula (A) which is disclosed in the aforesaid Japanese patent application No. 164,938/88 or its corresponding European patent application published specification No. 0350260A2 or its corresponding U.S. patent application Ser. No. 373,469, pending, and that the new compound of the general formula (I) and a pharmaceutically acceptable salt thereof are expectable as being useful for the cerebral drugs.
In addition, we have also succeeded in providing a process which can advantageously produce the novel compounds of the formula (I) on a commercial scale.